Actively Recruiting
A Phase 1 Study of Inhaled KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
Led by Krystal Biotech, Inc. · Updated on 2025-07-22
15
Participants Needed
3
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying KB408, a specially designed inhaled gene therapy using a non-replicating herpes simplex virus vector to deliver functional human SERPINA1 gene to the lungs of adults with alpha-1 antitrypsin deficiency (AATD). This trial targets adults aged 18 to 70 with specific genetic forms of AATD (PI*ZZ or PI*ZNull) to evaluate safety and how the treatment affects biological markers related to the disease. The study is a Phase 1 trial conducted by Krystal Biotech, Inc. to assess initial safety and pharmacodynamics of KB408. The study involves four groups: three single-dose groups receiving low, mid, or high doses of nebulized KB408, and one group receiving multiple doses at the mid-level dose. Participants receiving intravenous augmentation therapy must pause this treatment for at least 10 days before and during the repeat dose and high-dose groups. The investigational drug, KB408, is administered via nebulization to deliver the gene therapy directly to the airways. Participants will be monitored closely for safety over 2 to 3 months, including tracking adverse events, vital signs, lung function tests, ECGs, and laboratory tests. Researchers will also measure levels of alpha-1 antitrypsin and neutrophil elastase in blood and lungs to understand the treatment's biological effects. The study observes participants for changes from baseline to evaluate tolerability and pharmacodynamics of KB408 during and after dosing.
CONDITIONS
Brief Title
A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
Who Can Participate
Eligibility Criteria
You may qualify if you...
- The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board approved Informed Consent Form and be willing and able to follow study procedures.
- Age between 18 and 70 years at the time of informed consent.
- Genetically confirmed diagnosis of alpha-1 antitrypsin deficiency with a PIZZ or PIZNull genotype.
- For Cohort 2b and Cohort 3: Willingness to wash out intravenous AAT augmentation therapy for at least 10 days before screening and to remain off it during the study.
- For Cohort 2b and Cohort 3: Serum alpha-1 antitrypsin level below 11 micromolar at screening.
- Willingness to remain on a stable treatment regimen during the study.
- Resting oxygen saturation of 92% or higher on room air at screening.
- Clinically stable and in good general health except for alpha-1 antitrypsin deficiency as determined by the investigator.
You will not qualify if you...
- Forced expired volume in 1 second (FEV1) after bronchodilator less than 40% predicted at screening.
- Diffusing capacity of lungs for carbon monoxide (DLCO) less than 30% predicted within 2 years prior to screening or at screening.
- Known ongoing or history of significant lung problems other than alpha-1 antitrypsin deficiency.
- Pulmonary exacerbation within 42 days before first dose.
- Any new chronic therapy or change in ongoing therapy within 28 days before first dose.
- Participation in another interventional study or investigational agent treatment within 30 days or 5 half-lives before first dose.
- History of or listed for solid organ transplant or major lung surgery within 6 months before first dose.
- Any condition or illness that may affect ability to complete study or pose additional safety risk.
- Active oral herpes infection within 30 days before first dose.
- Significant liver dysfunction including elevated liver enzymes or bilirubin or clinical signs of cirrhosis.
- Smoking or use of tobacco, e-cigarettes, or recreational inhalants within 6 months before screening.
- Unwillingness to abstain from smoking or related products throughout the study.
- Positive urine cotinine test consistent with active smoking at screening, except when due to nicotine replacement therapy.
- Abnormal blood counts or chemistry that may interfere with safety assessment.
- Known noncompliance or unlikely to follow study protocol.
- Pregnant or nursing females.
- Unwillingness to follow contraception requirements per protocol.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 months for Cohorts 1, 2, and 3; up to 3 months for Cohort 2b
Participants receive a single or multiple doses of inhaled KB408 to treat alpha-1 antitrypsin deficiency, depending on cohort assignment.
1 dosing visit; follow-up visits depending on cohort assignment
Trial Site Locations
Total: 3 locations
1
University of Florida, Gainesville
Gainesville, Florida, United States, 32610
Actively Recruiting
2
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Actively Recruiting
3
Renovatio Clinical
The Woodlands, Texas, United States, 77380
Actively Recruiting
Research Team
D
David Sweet, MD, PhD
B
Brittani Agostini, RN, CCRC
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
4
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